This application for a Human Genome Center addresses two crucial needs of the Human Genome Project: 1) Innovative improvements in technology in order to allow completion of the project in a timely and cost-effective fashion; 2) Intensive and organized application of these technologies to families with genetic disease in order to maximize the medical benefits to the project. This P30 application is designed to expand and undergird the already strong existing research efforts in human genomics at the Universit of Michigan. The heart of the proposal is a series of seven cores: 1) Family Collection Core; 2) Genetic Marker Core; 3) Statistical Analysis Core; 4) Somatic Cell Genetics Core; 5) Library Core; 6) DNA Sequencing Core; and 7) Administrative Core. All of these are designed with heavy emphasis on technological advancement, with the intention of generating new approaches which will be of benefit to the Genome Project as a whole. This includes new methods for generating and testing microsatellite repeats, automation of genetic marker analysis, direct DNA sequencing of complex templates, megabase sequencing, generation of chromosome-specific linking libraries, novel cDNA cloning schemes, a variety of improvements in mathematical methods and data base management, and advances in somatic cell and in situ mapping technology. In addition, seven innovative pilot projects, which seek to advance genome technology are included as part of the proposal. The administrative component is designed to recruit new investigators into the field, to maximize communication amongst participants, and to provide oversight of the entire Center.